We characterized the DRB1 genotypes in a sample of 64 South American Indians drawn from populations in Chile, Colombia, and Ecuador. RESULTS No novel DRB1 alleles were found in the total of 17 different alleles characterized, indicating that rapid allelic generation does not occur at the DRB1 loci, in contrast to HLA-B. Comparison between Chilean and Colombian/Ecuadorian samples revealed no major differences in their allelic frequencies. In the combined Amerind sample the HLA-DRB1*0407 and HLA-DRB1*1402 alleles occurred in the highest frequencies (38% and 22%, respectively). Genetic distance measurement showed the HLA-DRB1 frequencies reported to agree with findings in other Amerind groups. The high frequencies of both DRB1*0407 and HLA-DRB1*1602 alleles, in conjunction with their absence in Siberian samples, suggest that migratory groups other than Siberians may have been involved in the peopling of the Americas. OBJECTIVE: To define HLA-DRB1 alleles expressed by South American Amerindians. FUTURE DIRECTIONS This data confirms the slow rate of evolution of the DRB1 locus in South America. KEY WORDS MHC, DRB1, South America